PB2403: THE FREQUENCY OF L265P MUTATION IN MYD88 GENE AT DIFFUSE LARGE B-CELL LYMPHOMA
Authors: Anastasiya Dubrovina, Ekaterina Tregubova, Elena Nazarova, Dmitry Diakonov, Svetlana Samarina
Journal: HemaSphere (2023)

Topic: 20. Lymphoma Biology & Translational Research Background: The L265P mutation is located in the Toll/interleukin-1 receptor domain of the myeloid differentiation factor 88 (MYD88) gene. This somatic mutation causes the conformational allosteric changes of a protein isoform. Then a series of molecular events leads to spontaneous signal transduction and constitutive activation of the NF-kB pathway. Many researchers come to a consensus that this molecular mechanism might be a basis of diffuse large B-cell lymphoma (DLBCL) development. According to the literature data, the occurrence of L265P mutation in MYD88 gene varies from 6.5 to 30.5% in DLBCL. The mutational status of MYD88 gene is different depending on the lymphoma’s immunohistochemical subtype and more frequent in non-GCB DLBCLs. However, the results of these investigations are inconsistent. The similar studies of the prevalence of oncogenic MYD88 mutation by the subtypes have not been published in available sources in Russian patients. Aims: To investigate the frequency of the L265P mutation in MYD88 gene in patients with various immunohistochemical subtypes of diffuse large-cell B-cell lymphoma. Methods: The mutational status of MYD88 gene has been explored in 86 patients with DLBCL. The cohort consisted of 37 males (43.0%) and 49 females (57.0%) with a median age at diagnosis of 59 (range, 27 to 82) years. A germinal subtype (GCB) of DLBCL and non-GCB subtype were classified based on immunohistochemical staining by C.P. Hans’ algorithm. Genomic DNA was isolated from the FFPE tumor tissues by “ExtractDNA FFPE” (“Evrogen”, Russia). The DNA was amplified by real-time PCR using the “SYBR Green PCR Master Mix” (“Applied Biosystems”, USA). The PCR products were detected using the real-time PCR “QuantStudio 5” (“Thermo Fisher Scientific Inc.”, Singapore). The patient mutational status was compared in different groups using Fisher’s exact test. P values of <0.05 were considered statistically significant. Results: According to Hans’s algorithm, a non-GCB immunohistochemical subtype was demonstrated in 52/ 86 (60.5%) cases, whereas a GCB immunophenotype of lymphoma was defined in 34/ 86 (39.5%) cases. The L265P mutation in MYD88 gene was detected in 13 of 86 (15.1%) samples of DNA. The occurrence of the mutation in a cohort of patients with non-GCB DLBCLs was identified in 23.1% (12/ 52) and in 2.9% (1/ 34) of cases with a GCB subtype. These results demonstrate that the frequency of L265P mutation in non-GCB lymphoma is significantly much higher than in GCB DLBCLs (p=0.01; OR = 9.90; 95%CI = 1.22–80.16). Reported by other researchers, the percentage of the aberrant MYD88 gene in a non-germinal variant amounts 22.0% and 3–5% in a germinal subtype. Summary/Conclusion: A difference between the frequency of mutation in non-germinal and germinal subtypes of DLBCL was more than eightfold. The mutational status of L265P MYD88 gene was significantly correlated with a non-GCB immunohistochemical subtype of DLBCL. The investigation of the significance of molecular genetic events in MYD88 gene will be continued. Keywords: Gene mutation, Real time PCR, Diffuse large B cell lymphoma, Molecular markers